Skip to main content
Erschienen in: Endocrine 3/2020

16.03.2020 | Original Article

Association of PPARγ gene expression with postprandial hypertriglyceridaemia and risk of type 2 diabetes mellitus

verfasst von: B. K. Mishra, B. D. Banerjee, V. Agrawal, S. V. Madhu

Erschienen in: Endocrine | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Peroxisome proliferator-activated receptor γ (PPARγ) gene is strongly associated with type 2 diabetes mellitus, as well as postprandial lipemia, and plays an important role in Wnt dependent adipogenesis in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). We aimed to study the expression of PPARγ gene in SAT and VAT to find out its correlation with postprandial hypertriglyceredemia and glucose intolerance.

Methods

Thirty subjects who were scheduled to undergo abdominal surgery were recruited in three groups (n = 10 in NGT, n = 10 in prediabetes, and n = 10 in T2DM). A standardized oral fat challenge was performed. Anthropometry, plasma glucose, HbA1c, and fasting serum insulin were also measured. SAT and VATs were collected during surgery for PPARγ gene expression studies by real-time PCR.

Results

PPARγ gene expression was 5.5-fold lower in T2DM and 1.7-fold lower in prediabetes as compared with NGT subjects in VAT. There was a significant negative correlation of expression of PPARγ gene in VAT {Tgauc (r = −0.57, p < 0.007), Peak Tg (r = −0.51, p < 0.01)} as well as in subcutaneous adipose tissue {Tgauc (r = −0.45, p < 0.02)} with PPTg responses measures.

Conclusion

Reduced adipocyte expression of PPARγ gene and the resultant postprandial hypertriglyceredemia is associated with greater risk of diabetes and prediabetes.
Literatur
3.
Zurück zum Zitat M. Aslam, S. Aggarwal, K.K. Sharma, V. Galav, Postprandial hypertriglyceridemia predicts development of insulin resistance glucoseintolerance and type 2 diabete. PLoS ONE 11(1), 1–15 (2016)CrossRef M. Aslam, S. Aggarwal, K.K. Sharma, V. Galav, Postprandial hypertriglyceridemia predicts development of insulin resistance glucoseintolerance and type 2 diabete. PLoS ONE 11(1), 1–15 (2016)CrossRef
4.
Zurück zum Zitat M. Axelsen, U. Smith, J.W. Eriksson, M.R. Taskinen, P.A. Jansson, Postprandial hypertriglyceridemia and insulin resistance in normoglycemic first-degree relatives of patients with type 2 diabetes. Ann. Intern. Med. 131(1), 27–31 (1999)PubMedCrossRef M. Axelsen, U. Smith, J.W. Eriksson, M.R. Taskinen, P.A. Jansson, Postprandial hypertriglyceridemia and insulin resistance in normoglycemic first-degree relatives of patients with type 2 diabetes. Ann. Intern. Med. 131(1), 27–31 (1999)PubMedCrossRef
6.
Zurück zum Zitat B.E. Rios-Gonzalez, K.E. Luevano-Ortega, A.M. Saldana-Cruz, J.R. Gonzalez-Garcia, M.T. Magana-Torres, Polymorphisms of seven genes involved in lipid metabolism in an unselected Mexican population. J. Genet. 90(3), e114–e119 (2011)PubMed B.E. Rios-Gonzalez, K.E. Luevano-Ortega, A.M. Saldana-Cruz, J.R. Gonzalez-Garcia, M.T. Magana-Torres, Polymorphisms of seven genes involved in lipid metabolism in an unselected Mexican population. J. Genet. 90(3), e114–e119 (2011)PubMed
7.
Zurück zum Zitat P. Perez-Martinez, J. Delgado-Lista, F. Perez-Jimenez, J. Lopez-Miranda, Update on genetics of postprandial lipemia. Atheroscler. Suppl. 11(1), 39–43 (2010)PubMedCrossRef P. Perez-Martinez, J. Delgado-Lista, F. Perez-Jimenez, J. Lopez-Miranda, Update on genetics of postprandial lipemia. Atheroscler. Suppl. 11(1), 39–43 (2010)PubMedCrossRef
8.
Zurück zum Zitat F. Cardona, S. Morcillo, M. Gonzalo-Marín, L. Garrido-Sanchez, M. Macias-Gonzalez, F.J. Tinahones, Pro12Ala sequence variant of the PPARG gene is associated with postprandial hypertriglyceridemia in non-E3/E3 patients with the metabolic syndrome. Clin. Chem. 52(10), 1920–1925 (2006)PubMedCrossRef F. Cardona, S. Morcillo, M. Gonzalo-Marín, L. Garrido-Sanchez, M. Macias-Gonzalez, F.J. Tinahones, Pro12Ala sequence variant of the PPARG gene is associated with postprandial hypertriglyceridemia in non-E3/E3 patients with the metabolic syndrome. Clin. Chem. 52(10), 1920–1925 (2006)PubMedCrossRef
9.
Zurück zum Zitat U. Edvardsson, PPARs in the Regulation of Gene Expression and Lipid Metabolism in the Liver, Department of Physiology Wallenberg Laboratory for Cardiovascular Research. The Sahlgrenska Academy at Göteborg University (Intellecta DocuSys AB, Göteborg, 2005) U. Edvardsson, PPARs in the Regulation of Gene Expression and Lipid Metabolism in the Liver, Department of Physiology Wallenberg Laboratory for Cardiovascular Research. The Sahlgrenska Academy at Göteborg University (Intellecta DocuSys AB, Göteborg, 2005)
11.
Zurück zum Zitat G. Castillo, S. Hauser, J.K. Rosenfield, B.M. Spiegelman, Role and regulation of PPARy during Adipogenesis. J. Anim. Sci. 77(Suppl 3), 9 (1999)CrossRef G. Castillo, S. Hauser, J.K. Rosenfield, B.M. Spiegelman, Role and regulation of PPARy during Adipogenesis. J. Anim. Sci. 77(Suppl 3), 9 (1999)CrossRef
13.
14.
Zurück zum Zitat P.J. Gianaros, K. Salomon, F. Zhou, J.F. Owens, L.H. Kuller, K.A.Matthews, Decreased Expression of adipogenic genes in obese subjects with type 2 diabetes. Obesity 67(4), 553–560 (2008) P.J. Gianaros, K. Salomon, F. Zhou, J.F. Owens, L.H. Kuller, K.A.Matthews, Decreased Expression of adipogenic genes in obese subjects with type 2 diabetes. Obesity 67(4), 553–560 (2008)
15.
Zurück zum Zitat Q. Guo, S.P. Sahoo, P.R. Wang, D.P. Milot, M.C. Ippolito, M.S. Wu et al. A novel peroxisome proliferator-activated receptor α/γ dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology 145(4), 1640–1648 (2004)PubMedCrossRef Q. Guo, S.P. Sahoo, P.R. Wang, D.P. Milot, M.C. Ippolito, M.S. Wu et al. A novel peroxisome proliferator-activated receptor α/γ dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology 145(4), 1640–1648 (2004)PubMedCrossRef
16.
Zurück zum Zitat A. Chawla, E.J. Schwarz, D.D. Dimaculangan, M.A. Lazar, Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135(2), 798–800 (1994)PubMedCrossRef A. Chawla, E.J. Schwarz, D.D. Dimaculangan, M.A. Lazar, Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135(2), 798–800 (1994)PubMedCrossRef
17.
Zurück zum Zitat U. Smith, B.B. Kahn, Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo lipogenesis and novel lipids. J. Intern. Med. 280(5), 465–475 (2016)PubMedPubMedCentralCrossRef U. Smith, B.B. Kahn, Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo lipogenesis and novel lipids. J. Intern. Med. 280(5), 465–475 (2016)PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat L.A. Muir, C.K. Neeley, K.A. Meyer, N.A. Baker, A.M. Brosius, A.R. Washabaugh et al. Adipose tissue fibrosis, hypertrophy, and hyperplasia: Correlations with diabetes in human obesity. Obesity 24(3), 597–605 (2016)PubMedCrossRef L.A. Muir, C.K. Neeley, K.A. Meyer, N.A. Baker, A.M. Brosius, A.R. Washabaugh et al. Adipose tissue fibrosis, hypertrophy, and hyperplasia: Correlations with diabetes in human obesity. Obesity 24(3), 597–605 (2016)PubMedCrossRef
19.
Zurück zum Zitat B. Gustafson, S. Hedjazifar, S. Gogg, A. Hammarstedt, U. Smith, Insulin resistance and impaired adipogenesis.Trends Endocrinol. Metab 26(4), 193–200 (2015)PubMedCrossRef B. Gustafson, S. Hedjazifar, S. Gogg, A. Hammarstedt, U. Smith, Insulin resistance and impaired adipogenesis.Trends Endocrinol. Metab 26(4), 193–200 (2015)PubMedCrossRef
20.
Zurück zum Zitat M.M. Ibrahim, Subcutaneous and visceral adipose tissue: structural and functional differences. Obes. Rev. 11(1), 11–18 (2010)PubMedCrossRef M.M. Ibrahim, Subcutaneous and visceral adipose tissue: structural and functional differences. Obes. Rev. 11(1), 11–18 (2010)PubMedCrossRef
21.
Zurück zum Zitat A. Lüdtke, J. Buettner, W. Wu, A. Muchir, A. Schroeter, S. Zinn-Justin et al. Peroxisome proliferator-activated receptor-γ C190S mutation causes partial lipodystrophy. J. Clin. Endocrinol. Metab. 92(6), 2248–2255 (2007)PubMedCrossRef A. Lüdtke, J. Buettner, W. Wu, A. Muchir, A. Schroeter, S. Zinn-Justin et al. Peroxisome proliferator-activated receptor-γ C190S mutation causes partial lipodystrophy. J. Clin. Endocrinol. Metab. 92(6), 2248–2255 (2007)PubMedCrossRef
22.
Zurück zum Zitat G. Medina-Gomez, S.L. Gray, L. Yetukuri, K. Shimomura, S. Virtue, M. Campbell et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 3(4), e64 (2007)PubMedPubMedCentralCrossRef G. Medina-Gomez, S.L. Gray, L. Yetukuri, K. Shimomura, S. Virtue, M. Campbell et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 3(4), e64 (2007)PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat C. Knouff, J. Auwerx, Peroxisome proliferator-activated receptor-γ calls for activation in moderation: Lessons from genetics and pharmacology. Endocr. Rev. 25(6), 899–918 (2004)PubMedCrossRef C. Knouff, J. Auwerx, Peroxisome proliferator-activated receptor-γ calls for activation in moderation: Lessons from genetics and pharmacology. Endocr. Rev. 25(6), 899–918 (2004)PubMedCrossRef
25.
Zurück zum Zitat S.V. Madhu, M. Aslam, V. Galav, S.K. Bhattacharya, A.A. Jafri, Atorvastatin prevents type 2 diabetes mellitus-an experimental study. Eur. J. Pharm. 728(April), 135–140 (2014)CrossRef S.V. Madhu, M. Aslam, V. Galav, S.K. Bhattacharya, A.A. Jafri, Atorvastatin prevents type 2 diabetes mellitus-an experimental study. Eur. J. Pharm. 728(April), 135–140 (2014)CrossRef
26.
Zurück zum Zitat S.J. Li, Y.Y. Wu, W. Li, S.J. Wang, Y.M. Fan, Ultrastructural observation in a case of mucinous nevus. J. Ger. Soc. Dermatol. 16(6), 778–780 (2018) S.J. Li, Y.Y. Wu, W. Li, S.J. Wang, Y.M. Fan, Ultrastructural observation in a case of mucinous nevus. J. Ger. Soc. Dermatol. 16(6), 778–780 (2018)
27.
Zurück zum Zitat D. Care, S.S. Suppl, Classification and diagnosis of diabetes: standards of medical care in Diabetesd2018. Diabetes Care 41(January), S13–S27 (2018) D. Care, S.S. Suppl, Classification and diagnosis of diabetes: standards of medical care in Diabetesd2018. Diabetes Care 41(January), S13–S27 (2018)
28.
Zurück zum Zitat K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4), 402–408 (2001)CrossRef K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4), 402–408 (2001)CrossRef
29.
Zurück zum Zitat C.J. Yen, B.A. Beamer, C. Negri, K. Silver, K.A. Brown, D.P. Yarnall et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem. Biophys. Res. Commun. 241(2), 270–274 (1997)PubMedCrossRef C.J. Yen, B.A. Beamer, C. Negri, K. Silver, K.A. Brown, D.P. Yarnall et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem. Biophys. Res. Commun. 241(2), 270–274 (1997)PubMedCrossRef
30.
Zurück zum Zitat S.V. Madhu, S. Kant, S. Srivastava, R. Kant, S.B. Sharma, D.P. Bhadoria, Postprandial lipaemia in patients with impaired fasting glucose, impaired glucose tolerance and diabetes mellitus. Diabetes Res. Clin. Pract. 80(3), 380–385 (2008)PubMedCrossRef S.V. Madhu, S. Kant, S. Srivastava, R. Kant, S.B. Sharma, D.P. Bhadoria, Postprandial lipaemia in patients with impaired fasting glucose, impaired glucose tolerance and diabetes mellitus. Diabetes Res. Clin. Pract. 80(3), 380–385 (2008)PubMedCrossRef
31.
Zurück zum Zitat K. Fujiki, F. Kano, K. Shiota, M. Murata, Expression of the peroxisome proliferator activated receptor γ gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes. BMC Biol. 7, 1–14 (2009)CrossRef K. Fujiki, F. Kano, K. Shiota, M. Murata, Expression of the peroxisome proliferator activated receptor γ gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes. BMC Biol. 7, 1–14 (2009)CrossRef
32.
Zurück zum Zitat A. Vidal-Puig, M. Jimenez-Liñan, B.B. Lowell, A. Hamann, E. Hu, B. Spiegelman et al. Regulation of PPARγ gene expression by nutrition and obesity in rodents. J. Clin. Investig. 97(11), 2553–2561 (1996)PubMedCrossRef A. Vidal-Puig, M. Jimenez-Liñan, B.B. Lowell, A. Hamann, E. Hu, B. Spiegelman et al. Regulation of PPARγ gene expression by nutrition and obesity in rodents. J. Clin. Investig. 97(11), 2553–2561 (1996)PubMedCrossRef
33.
Zurück zum Zitat C. Leyvraz, C. Verdumo, M. Suter, A. Paroz, J.M. Calmes, P.M. Marques-Vidal et al. Changes in gene expression profile in human subcutaneous adipose tissue during significant weight loss. Obes. Facts 5(3), 440–451 (2012)PubMedCrossRef C. Leyvraz, C. Verdumo, M. Suter, A. Paroz, J.M. Calmes, P.M. Marques-Vidal et al. Changes in gene expression profile in human subcutaneous adipose tissue during significant weight loss. Obes. Facts 5(3), 440–451 (2012)PubMedCrossRef
34.
Zurück zum Zitat T.O. Hammes, Costa CDS, F. Rohden, R. Margis, AlmeidaJ.C. De, A.V. Padoin et al. Parallel down-regulation of FOXO1, PPARγ and adiponectin mRNA expression in visceral adipose tissue of class III obese individuals. Obes. Facts 5(3), 452–459 (2012)PubMedCrossRef T.O. Hammes, Costa CDS, F. Rohden, R. Margis, AlmeidaJ.C. De, A.V. Padoin et al. Parallel down-regulation of FOXO1, PPARγ and adiponectin mRNA expression in visceral adipose tissue of class III obese individuals. Obes. Facts 5(3), 452–459 (2012)PubMedCrossRef
35.
Zurück zum Zitat A. Wagener, H.F. Goessling, A.O. Schmitt, S. Mauel, A.D. Gruber, R. Reinhardt et al. Genetic and diet effects on Ppar-α and Ppar-γ signaling pathways in the Berlin Fat Mouse Inbred line with genetic predisposition for obesity. Lipids Health Dis. 9(ii), 1–10 (2010) A. Wagener, H.F. Goessling, A.O. Schmitt, S. Mauel, A.D. Gruber, R. Reinhardt et al. Genetic and diet effects on Ppar-α and Ppar-γ signaling pathways in the Berlin Fat Mouse Inbred line with genetic predisposition for obesity. Lipids Health Dis. 9(ii), 1–10 (2010)
36.
Zurück zum Zitat M. Hatami, M. Saidijam, R. Yadegarzari, S. Borzuei, A. Soltanian, M.S. Arian et al. Peroxisome proliferator-activated receptor-gamma gene expression and its association with oxidative stress in patients with metabolic syndrome. Chonnam Med. J. 52(3), 201–206 (2016)PubMedPubMedCentralCrossRef M. Hatami, M. Saidijam, R. Yadegarzari, S. Borzuei, A. Soltanian, M.S. Arian et al. Peroxisome proliferator-activated receptor-gamma gene expression and its association with oxidative stress in patients with metabolic syndrome. Chonnam Med. J. 52(3), 201–206 (2016)PubMedPubMedCentralCrossRef
37.
Zurück zum Zitat K. Ruschke, L. Fishbein, A. Dietrich, N. Klöting, A. Tönjes, A. Oberbach, et al. Markers and mediates beneficial effects of physical training. Eur J Endocrinol 162(3), 515–523 (2010)PubMedCrossRef K. Ruschke, L. Fishbein, A. Dietrich, N. Klöting, A. Tönjes, A. Oberbach, et al. Markers and mediates beneficial effects of physical training. Eur J Endocrinol 162(3), 515–523 (2010)PubMedCrossRef
39.
Zurück zum Zitat Y. Lecarpentier, V. Claes, A. Vallée, J.L. Hébert, Interactions between PPAR gamma and the canonical Wnt/beta-catenin pathway in type 2 diabetes and colon cancer. PPAR Res. 2017, 1–9 (2017) Y. Lecarpentier, V. Claes, A. Vallée, J.L. Hébert, Interactions between PPAR gamma and the canonical Wnt/beta-catenin pathway in type 2 diabetes and colon cancer. PPAR Res. 2017, 1–9 (2017)
40.
Zurück zum Zitat D. Ren, T.N. Collingwood, E.J. Rebar, A.P. Wolffe, H.S. Camp, PPARγ knockdown by engineered transcription factors: Exogenous PPARγ2 but not PPARγ1 reactivates adipogenesis. Genes Dev. 16(1), 27–32 (2002)PubMedPubMedCentralCrossRef D. Ren, T.N. Collingwood, E.J. Rebar, A.P. Wolffe, H.S. Camp, PPARγ knockdown by engineered transcription factors: Exogenous PPARγ2 but not PPARγ1 reactivates adipogenesis. Genes Dev. 16(1), 27–32 (2002)PubMedPubMedCentralCrossRef
Metadaten
Titel
Association of PPARγ gene expression with postprandial hypertriglyceridaemia and risk of type 2 diabetes mellitus
verfasst von
B. K. Mishra
B. D. Banerjee
V. Agrawal
S. V. Madhu
Publikationsdatum
16.03.2020
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 3/2020
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-020-02257-w

Weitere Artikel der Ausgabe 3/2020

Endocrine 3/2020 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.